[go: up one dir, main page]

WO2009158698A9 - Administration ciblée de sondes d'imagerie pour une imagerie cellulaire in vivo - Google Patents

Administration ciblée de sondes d'imagerie pour une imagerie cellulaire in vivo Download PDF

Info

Publication number
WO2009158698A9
WO2009158698A9 PCT/US2009/049023 US2009049023W WO2009158698A9 WO 2009158698 A9 WO2009158698 A9 WO 2009158698A9 US 2009049023 W US2009049023 W US 2009049023W WO 2009158698 A9 WO2009158698 A9 WO 2009158698A9
Authority
WO
WIPO (PCT)
Prior art keywords
nitroxide
liposome
imaging
cells
interest
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2009/049023
Other languages
English (en)
Other versions
WO2009158698A3 (fr
WO2009158698A2 (fr
Inventor
Joseph P.Y. Kao
Scott R. Burks
Gerald R. Rosen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
The University of Maryland Biotechnology Institute
Original Assignee
The University of Maryland Biotechnology Institute
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The University of Maryland Biotechnology Institute filed Critical The University of Maryland Biotechnology Institute
Publication of WO2009158698A2 publication Critical patent/WO2009158698A2/fr
Publication of WO2009158698A3 publication Critical patent/WO2009158698A3/fr
Publication of WO2009158698A9 publication Critical patent/WO2009158698A9/fr
Priority to US12/975,655 priority Critical patent/US10202342B2/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B27/00—Optical systems or apparatus not provided for by any of the groups G02B1/00 - G02B26/00, G02B30/00
    • G02B27/10—Beam splitting or combining systems
    • G02B27/14—Beam splitting or combining systems operating by reflection only
    • G02B27/145—Beam splitting or combining systems operating by reflection only having sequential partially reflecting surfaces
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B23/00—Telescopes, e.g. binoculars; Periscopes; Instruments for viewing the inside of hollow bodies; Viewfinders; Optical aiming or sighting devices
    • G02B23/02—Telescopes, e.g. binoculars; Periscopes; Instruments for viewing the inside of hollow bodies; Viewfinders; Optical aiming or sighting devices involving prisms or mirrors
    • G02B23/08—Periscopes
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B27/00—Optical systems or apparatus not provided for by any of the groups G02B1/00 - G02B26/00, G02B30/00
    • G02B27/10—Beam splitting or combining systems
    • G02B27/1006—Beam splitting or combining systems for splitting or combining different wavelengths
    • G02B27/1013—Beam splitting or combining systems for splitting or combining different wavelengths for colour or multispectral image sensors, e.g. splitting an image into monochromatic image components on respective sensors
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B27/00—Optical systems or apparatus not provided for by any of the groups G02B1/00 - G02B26/00, G02B30/00
    • G02B27/10—Beam splitting or combining systems
    • G02B27/14—Beam splitting or combining systems operating by reflection only
    • G02B27/141—Beam splitting or combining systems operating by reflection only using dichroic mirrors
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B17/00—Systems with reflecting surfaces, with or without refracting elements
    • G02B17/02—Catoptric systems, e.g. image erecting and reversing system
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B7/00—Mountings, adjusting means, or light-tight connections, for optical elements
    • G02B7/20—Light-tight connections for movable optical elements
    • G02B7/24—Pivoted connections

Definitions

  • an object of the present invention to provide for a system for the detection of a biological cells or tissue of interest comprising an encapsulated stable free radical probe within a liposome, wherein the liposome has been conjugated to targeting ligand specific to the biological cells or tissue of interest.
  • the present invention relates to an imaging complex for identifying targeted tissue of interest, the imaging complex comprising: a. a liposome; b. a detection probe encapsulated within the liposome, wherein the detection probe is concentrated to a level causing self quenching with no identifiable signal; and c. a targeting ligand positioned on the surface of the liposome and having affinity for a receptor on the targeted tissue of interest, and wherein the detection probe is a nitroxide, triarylmethyl (trityl) radicals, precursor or derivative thereof.
  • Figure 13 shows that the incubation with anti-Her2 immunoliposomes containing Rhod-PE and encapsulating CF generates bright intracellular signals in Hc7 cells, but not MCF7 or CVl cells.
  • Panels a, d, and g are transmitted light images; panels b, e, and h show fluorescence in the fluorescein channel; panels c, f, and i show fluorescence in the rhodamine channel.
  • HER2-overexpressing Hc7 cells (a-c) avidly endocytose immunoliposomes, resulting in de-quenching of CF to generate bright intracellular fluorescence.
  • MCF7 cells (d-f) express a physiological level of HER2 and endocytose fewer liposomes, giving rise to only feeble fluorescence.
  • CVl cells (g-i) which express no HER2, exhibit no fluorescence.
  • Intracellular refers to the area within the plasma membrane of a cell, including the protoplasm, cytoplasm and/or nucleoplasm, and/or the luminal space of intracellular organelles.
  • Intracellular delivery refers to the delivery of photoactive agents, image contrast-enhancing agents, bioactive agents and/or targeting ligands into the area within the plasma membrane of a cell.
  • Cell refers to any one of the minute protoplasmic masses which make up organized tissue, comprising a mass of protoplasm surrounded by a membrane, including nucleated and unnucleated cells and organelles.
  • Antibodies can be fragmented using conventional techniques as described herein and the fragments screened for utility in the same manner as described for whole antibodies.
  • a Fab fragment of an immunoglobulin molecule is a multimeric protein consisting of the portion of an immunoglobulin molecule containing the immunologically active portions of an immunoglobulin heavy chain and an immunoglobulin light chain covalently coupled together and capable of specifically combining with an antigen.
  • Fab and Fc fragments can be prepared by proteolytic digestion of substantially intact immunoglobulin molecules with papain using methods that are well known in the art. However, a Fab or Fc fragment may also be prepared by expressing in a suitable host cell the desired portions of immunoglobulin heavy chain and immunoglobulin light chain using methods known in the art.
  • a liposome vesicle including but not limited to the nitroxide structures shown below.
  • the size of the liposomes of the present invention will depend upon the intended use and the size of the nitroxide inclusion. Sizing also serves to modulate resultant liposomal biodistribution and clearance which can be determined by one skilled in the art.
  • the size of the liposomes can be adjusted, if desired, by procedures known to one skilled in the art, such as shaking, microemulsification, vortexing, filtration, repeated freezing and thawing cycles, extrusion, extrusion under pressure through pores of a defined size, sonication, homogenization, the use of a laminar stream of a core of liquid introduced into an immiscible sheath of liquid. Extrusion under pressure through pores of defined size is a preferred method of adjusting the size of the liposomes.
  • HER2 immunostaining MCF7 and Hc 7 cells were cultured on 25-mm No. 1 glass coverslips for 24 - 48 hr. All steps in the staining procedure were at room temperature; following each step, cells were washed three times with DBPS. Cells were fixed with 4% paraformaldehyde in DPBS (final pH 7.4) for 20 min. Blocking of non-specific antigen sites was done with 10% normal rabbit serum in DBPS for 1 hr. Primary antibodies in DBPS were incubated with cells for 3 hr.
  • Example 1 -Glass tubes used as imaging phantom device [0099]
  • Example 1 -Glass tubes used as imaging phantom device [0099]
  • MCF7 breast tumor cells were stably transfected to overexpress the HER2 receptor.
  • the resulting Hc7 transfectants were analyzed by western blot for HER2 expression, as shown in Figure 10. Although Hc7 cells exhibit a high level of total HER2 expression compared to MCF7 cells, western blotting does not provide information regarding subcellular localization of protein.
  • Intact trastuzumab readily binds HER2 with high specificity, but attachment to liposomes requires proteolytic cleavage and reduction of the antibody to form the crosslinkable thiol-exposed Fab' fragment.
  • Hc7, MCF7, and CVl cells were immunostained as outlined above, with the exception that primary antibodies were Fab' fragments whose exposed reactive thiol groups had been inactivated with maleimide (Figure 12). Hc7 cells still exhibit -35-100 times greater FITC fluorescence than MCF7 cells (t-test p ⁇ 0.01).
  • ANOVA is performed on the combined data from Figures 1 IA and 12A, post-hoc analysis confirms the previous t- test results — regardless of which primary antibody was used, immunofluorescence differed significantly between Hc7 and MCF7 cells.
  • SCID mice to form tumors that grew rapidly during a six week period as shown in Figure 11.
  • the stealth liposomes of the present invention having a Fab' with affinity for the HER-2 receptor, bind to the HER-2 receptor, the complex is endocytosed and lysed within the cell.
  • liposomes since liposomes must target tumors from the circulation, their ultimate uptake into tumor cells depends on tumor vascularization. While previous studies examining the pharmacodynamics of liposomes in tumor models suggests a relatively uniform micro- distribution of immunoliposomes within tumors (Kirpotin et al, 2006), the macro- distribution could be inhomogeneous due to any necrosis toward the center of tumor. Thus, it is possible that only some fraction of the tumor volume is accessible to liposomes.

Landscapes

  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Astronomy & Astrophysics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Optical Elements Other Than Lenses (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention porte sur des sondes d'imagerie comprenant des immunoliposomes qui encapsulent des concentrations auto-désactivantes de radicaux libres stables ou d'agents de contraste à relaxivité élevée, tels que des nitroxydes ou des radicaux trityle, les immunoliposomes comprenant un ligand de ciblage, positionné sur la surface des immunoliposomes et ayant une affinité pour un tissu ciblé.
PCT/US2009/049023 2008-06-27 2009-06-29 Administration ciblée de sondes d'imagerie pour une imagerie cellulaire in vivo Ceased WO2009158698A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US12/975,655 US10202342B2 (en) 2008-06-27 2010-12-22 Targeted delivery of imaging probes for in vivo cellular imaging

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US7648408P 2008-06-27 2008-06-27
US61/076,484 2008-06-27

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/975,655 Continuation-In-Part US10202342B2 (en) 2008-06-27 2010-12-22 Targeted delivery of imaging probes for in vivo cellular imaging

Publications (3)

Publication Number Publication Date
WO2009158698A2 WO2009158698A2 (fr) 2009-12-30
WO2009158698A3 WO2009158698A3 (fr) 2010-04-29
WO2009158698A9 true WO2009158698A9 (fr) 2010-06-17

Family

ID=41444931

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US2009/048519 Ceased WO2009158434A1 (fr) 2008-06-27 2009-06-24 Prisme semi-réfléchissant à séparation de longueur d’onde
PCT/US2009/049023 Ceased WO2009158698A2 (fr) 2008-06-27 2009-06-29 Administration ciblée de sondes d'imagerie pour une imagerie cellulaire in vivo

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/US2009/048519 Ceased WO2009158434A1 (fr) 2008-06-27 2009-06-24 Prisme semi-réfléchissant à séparation de longueur d’onde

Country Status (4)

Country Link
US (1) US8184375B2 (fr)
EP (1) EP2307917B1 (fr)
JP (1) JP2011526377A (fr)
WO (2) WO2009158434A1 (fr)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009158434A1 (fr) 2008-06-27 2009-12-30 Panavision Federal Systems, Llc Prisme semi-réfléchissant à séparation de longueur d’onde
US8988564B2 (en) * 2011-09-09 2015-03-24 Apple Inc. Digital camera with light splitter
US9299118B1 (en) * 2012-04-18 2016-03-29 The Boeing Company Method and apparatus for inspecting countersinks using composite images from different light sources
US20140111813A1 (en) * 2012-10-19 2014-04-24 Hamar Laser Instruments, Inc. Optical assembly and laser alignment apparatus
US20140111866A1 (en) * 2012-10-19 2014-04-24 Hamar Laser Instruments, Inc. Optical assembly and laser alignment apparatus
CN103197066B (zh) * 2013-03-07 2015-12-23 美国纳米材料创新有限公司 一种免疫脂质体生物芯片、其制备方法及其在生物检测中的应用
US9709811B2 (en) 2013-08-14 2017-07-18 Kla-Tencor Corporation System and method for separation of pump light and collected light in a laser pumped light source
DE102015101847B4 (de) * 2015-02-10 2017-11-02 Eyesense Gmbh Strahlteiler und Anordnung zur Untersuchung einer mittels elektromagnetischer Strahlung anregbaren Probe
US10075646B2 (en) 2015-11-30 2018-09-11 Sensors Unlimited, Inc. Sensor systems and methods
NL2017973B1 (en) * 2016-12-09 2018-06-19 Quest Photonic Devices B V Dichroic prism assembly with four or five channels
WO2018132490A1 (fr) 2017-01-12 2018-07-19 Canon U.S.A., Inc. Endoscope à visualisation avant spectralement codée et endoscope à multi-visualisation spectralement codée, sonde, et appareil d'imagerie
US10144707B2 (en) * 2017-03-07 2018-12-04 Organic Energy Devices (Oed) Tritiated nitroxides and uses thereof
CN206552113U (zh) * 2017-03-25 2017-10-13 何亦宗 一种隐形四棱柱
US10286957B2 (en) 2017-03-25 2019-05-14 Yizong He Invisible frame for automobile windshield and side windows
US10634982B2 (en) * 2017-09-01 2020-04-28 Panasonic Intellectual Property Management Co., Ltd. Light source device and projection display apparatus
KR20190054472A (ko) 2017-11-13 2019-05-22 삼성전자주식회사 전반사 프리즘 유닛, 이를 포함하는 전반사 프리즘 어셈블리 및 라인 빔 형성 장치
DE102018129832B4 (de) 2017-12-04 2020-08-27 Leica Microsystems Cms Gmbh Mikroskopsystem und Verfahren zur mikroskopischen Abbildung
DE102018129833B4 (de) 2017-12-04 2020-01-02 Leica Microsystems Cms Gmbh Mikroskopsystem, Detektionseinheit für Mikroskopsystem und Verfahren zur mikroskopischen Abbildung einer Probe
DE102018124129A1 (de) * 2017-12-04 2019-06-06 Leica Microsystems Cms Gmbh Mikroskopsystem und Verfahren zur mikroskopischen Abbildung mit einem solchen Mikroskopsystem
DE102020120198B4 (de) 2020-07-30 2022-07-14 Leica Microsystems Cms Gmbh Verfahren zur Montage einer Detektionsanordnung für ein Mikroskopsystem
CN119935315A (zh) * 2025-01-24 2025-05-06 上海交通大学 一种高温环境水雾穿透三波长测温装置与方法

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR596542A (fr) * 1924-04-15 1925-10-26 Dispositif pour la prise de vues et la projection de photographies, en particulier de vues cinématographiques en couleurs naturelles
US2737076A (en) * 1952-06-12 1956-03-06 Technicolor Motion Picture Method of making optical prism
NL254460A (fr) * 1960-08-02
NL6616679A (fr) * 1966-11-26 1968-05-27
DE1597210A1 (de) * 1967-08-31 1969-10-02 Fernseh Gmbh Optisches System fuer Farbfernsehgeraete
NL160398C (nl) 1969-03-25 1979-10-15 Philips Nv Kleurensplitsend prismastelsel.
DE2012480A1 (de) 1970-03-17 1971-10-07 Optische Werke G Rodenstock 8000 München Prismenanordnung fur additive Färb aufnahme
JPS5136090B1 (fr) * 1971-04-17 1976-10-06
DE2235873A1 (de) 1972-07-21 1973-02-01 Bosch Fernsehanlagen Farb-fernsehkamera
GB1401476A (en) * 1972-09-19 1975-07-16 Rank Organisation Ltd Optical beam splitting systems
JPS49133042A (fr) * 1973-04-09 1974-12-20
JPS5342370B2 (fr) * 1973-07-02 1978-11-10
GB1474699A (en) * 1973-12-11 1977-05-25 Rank Organisation Ltd Beam splitting prism assembly
NL7400148A (nl) * 1974-01-07 1975-07-09 Philips Nv Kleurensplitsend prismastelsel met enige opper- en die aan dichroitische lagen grenzen.
JPS5192122A (fr) 1975-02-10 1976-08-12
NL7511838A (nl) * 1975-10-09 1977-04-13 Philips Nv Kleurscheidende prismacombinatie.
US4268119A (en) * 1979-01-22 1981-05-19 Bell & Howell Company Color-separating optical system
NL8006609A (nl) * 1980-12-04 1982-07-01 Philips Nv Televisiecamera voorzien van een achter het objectief geplaatst kleurensplitsend stelsel.
US4425028A (en) * 1981-12-28 1984-01-10 Hughes Aircraft Company High efficiency optical tank for three color liquid crystal light valve image projection with color selective prepolarization and single projection lens
US4687301A (en) * 1985-07-12 1987-08-18 Hughes Aircraft Company Full-color projector system with a tricolor-separating prism
US4690526A (en) * 1985-09-12 1987-09-01 Hughes Aircraft Company Prism assembly for a single light valve full-color projector
JPH0660963B2 (ja) 1986-09-17 1994-08-10 松下電器産業株式会社 色分解プリズム
JPS63167318A (ja) * 1986-12-27 1988-07-11 Canon Inc 実体顕微鏡
NL8802517A (nl) * 1988-10-13 1990-05-01 Philips Nv Beeldprojektie-inrichting.
NL8902205A (nl) * 1989-09-01 1991-04-02 Philips Nv Projektiesysteem.
US5725839A (en) * 1993-08-16 1998-03-10 Hsia; Jen-Chang Compositions and methods utilizing nitroxides in combination with biocompatible macromolecules for ERI or MRI
JPH07281131A (ja) * 1994-04-04 1995-10-27 Mitsubishi Electric Corp 赤外線撮像装置
JP3507122B2 (ja) 1994-04-11 2004-03-15 キヤノン株式会社 色分解光学系、あるいは色分解光学系を有するテレビカメラ
US5644432A (en) 1995-01-17 1997-07-01 Ibm Corporation Three prism color separator
US5671047A (en) * 1995-05-15 1997-09-23 Bio-Rad Laboratories Laser beamsplitter for generating a plurality of parallel beams
JPH09197341A (ja) * 1996-01-11 1997-07-31 Nikon Corp 投写表示装置
SK149398A3 (en) * 1996-05-03 2000-02-14 Finmeccanica Spa Panoramic periscope
US5867617A (en) * 1997-05-19 1999-02-02 E-Tek Dynamics, Inc. High-reliability MXN fiber optic switches
US6144498A (en) 1998-06-11 2000-11-07 Optical Coating Laboratory, Inc. Color separation prism assembly and method for making same
US6280037B1 (en) * 1999-02-26 2001-08-28 Intel Corporation Aligning images of a projection system
JP2000275545A (ja) * 1999-03-29 2000-10-06 Fuji Photo Optical Co Ltd パノラマ観察光学系
US6644813B1 (en) * 2002-01-04 2003-11-11 Raytheon Company Four prism color management system for projection systems
IL148804A (en) * 2002-03-21 2007-02-11 Yaacov Amitai Optical device
DE10316242A1 (de) * 2003-04-09 2004-10-28 Carl Zeiss Umlenksystem für eine Beobachtungseinrichtung sowie Beobachtungseinrichtung
EP1846799A4 (fr) * 2005-02-09 2011-01-26 Inc Wavien Combinaison a effacite en etendue de sources de lumiere multiples
US7969832B2 (en) * 2006-02-02 2011-06-28 Oracle America, Inc. Optical tape drive systems
WO2009158434A1 (fr) 2008-06-27 2009-12-30 Panavision Federal Systems, Llc Prisme semi-réfléchissant à séparation de longueur d’onde

Also Published As

Publication number Publication date
WO2009158698A3 (fr) 2010-04-29
JP2011526377A (ja) 2011-10-06
EP2307917B1 (fr) 2019-02-20
EP2307917A4 (fr) 2016-05-25
US8184375B2 (en) 2012-05-22
EP2307917A1 (fr) 2011-04-13
WO2009158434A1 (fr) 2009-12-30
US20090323192A1 (en) 2009-12-31
WO2009158698A2 (fr) 2009-12-30

Similar Documents

Publication Publication Date Title
WO2009158698A9 (fr) Administration ciblée de sondes d'imagerie pour une imagerie cellulaire in vivo
Kirpotin et al. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models
AU2018269742B2 (en) Nano-enabled immunotherapy in cancer
Pan et al. Synthesis of cetuximab-immunoliposomes via a cholesterol-based membrane anchor for targeting of EGFR
Ogawa et al. In vivo target-specific activatable near-infrared optical labeling of humanized monoclonal antibodies
Marqués-Gallego et al. Ligation strategies for targeting liposomal nanocarriers
Song et al. Novel peptide ligand directs liposomes toward EGF‐R high‐expressing cancer cells in vitro and in vivo
US11433143B2 (en) Nano-enabled immunotherapy in cancer
US9801943B2 (en) Method for in vivo targeting of nanoparticles via bioorthogonal copper-free click chemistry
CN101855237B (zh) 肽配体定向药物递送
US20100209352A1 (en) Synthesis and conjugation of iron oxide nanoparticles to antibodies for targeting specific cells using fluorescence and mr imaging techniques
CN103990151A (zh) 一种磁共振成像造影剂及其制备方法和应用
Azimizonuzi et al. A state-of-the-art review of the recent advances of theranostic liposome hybrid nanoparticles in cancer treatment and diagnosis
US10202342B2 (en) Targeted delivery of imaging probes for in vivo cellular imaging
Burks et al. Anti-HER2 immunoliposomes for selective delivery of electron paramagnetic resonance imaging probes to HER2-overexpressing breast tumor cells
TW201804987A (zh) 以艾弗林受體Ａ２（ＥｐｈＡ２）為標靶的歐洲紫杉醇產生之奈米微脂體組成物
Burks et al. Cellular uptake of electron paramagnetic resonance imaging probes through endocytosis of liposomes
CN108697693B (zh) 用于靶向、成像和治疗前列腺癌的肽共轭的纳米粒子
Ding et al. Sensitive photoacoustic/magnetic resonance dual imaging probe for detection of malignant tumors
US20120258038A1 (en) Uses of apoptotic cell-targeting peptides, label substances and liposomes containing a therapeutic agent for preventing, treating or therapeutically diagnosing apoptosis-related diseases
EP4353267A1 (fr) Liposome conjugué à un anticorps
US6379647B2 (en) Use of mononuclear phagocytes in in vivo imaging of hypoxic/ischaemic tissue
EP4212179A1 (fr) Complexe et photoimmunothérapie
Shimizu et al. Liposomes conjugated with a pilot molecule
WO2019165101A1 (fr) Combinaison de produits chimiques orthogonaux pour la préparation de nanoparticules multiplexées

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09771229

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09771229

Country of ref document: EP

Kind code of ref document: A2